This project is a continuation of an ongoing program consisting of a comprehensive study of the molecular biology of bacterial plasmids. Inasmuch as its long-term goal is a fundamental understanding of the molecular basis of the plasmid state, it necessarily encompasses a number of sub-projects dealing with operationally separable aspects of the overall problem. The test system is, for the most part, Staphylococcus aureus and a group of its plasmids that are responsible for resistance to a variety of antibiotics and heavy metals. Other organisms will be used when required by a particular line of investigation: it will be important to confirm and in some cases extend the S. aureus findings in E. coli. Among the major aspects of the project are (a) investigation into the prevalence and dissemination among gram-positive organisms of particular plasmid prototypes and certain of their genes: (b) physical and genetic studies of plasmid structure; (c) genetic and molecular studies of plasmid replication and partition and the control of these processes; (d) molecular studies of plasmid transfer by transduction and of the integration of plasmids into other replicons; and (e) analysis of the control of plasmid transcription insofar as there may exist such controls that are characteristic of the plasmid state.